This program project grant is committed to the development of new chemotherapeutic strategies. It tightly integrates laboratory investigators with clinician-scientists resulting in the propagation of ideas directly from the laboratory into clinical trial. The Section of Medical Oncology has been realigned to promote this program through Disease Specific Units. Additional backing comes from the Pharmacology Program Project Grant (Dr. Alan Sartorelli, P.I.) which explores more speculative aspects of tumor biology and metabolism to identify leads for developmental therapeutics. The Comprehensive Cancer Center provides additional support through its core facilities. Dr. Sartorelli, Director, and Dr. Hait, Associate Director for Clinical Affairs, are direct links with this program. Specific projects and their direct applications include: 6- thioguanine and hypoxanthine to induce differentiation of leukemic cells- Leukemia Unia (Sartorelli, Todd); the calcium messenger system in squamous cell differentiation - Head and Neck Unit (Reiss); synergism between BCNU and thymidine-Neuro-oncology and Lymphoma Units (Prusoff, Cooper); new agents to overcome multidrug resistance - Breast Unit and others (Hait, Handschumacher); biochemical aspects to hepatic metastases - GI Unit (Handschumacher); Genetic transfer of drug-resistance-all units (Cadman). The Clinical Trials project provides the clinical outlet for the laboratory programs. The program is supported by four Cores, Administrative, Biostatistics, Clinical Pharmacology, and Clinical Diagnostics.